PROJECT SUMMARY/ ABSTRACT One in three Americans is obese, creating an annual financial burden in excess of 140 billion dollars. Obesity is caused by a combination of excessive food intake, a lack of physical activity, and genetic predisposition. These factors are thought to converge on neural circuits in the brain that control energy balance, but how these circuits are regulated in vivo remains poorly understood. A deeper understanding of these circuits has the potential to suggest novel therapeutic approaches for the treatment of obesity. The paraventricular hypothalamus (PVH) is one of the most important structures in the brain for the regulation of food intake. The PVH contains a great diversity of neural cell types, and the in vivo dynamics of these cell types during behavior is unknown. In the proposed experiments, we will use a state-of-the-art approach for two-photon, deep-brain calcium imaging to measure for the first time how feeding-regulatory neurons in PVH are controlled by sensory, hormonal, and circuit-based signals. These experiments will reveal logic by which hunger and satiety are encoded in key neurons in the brain that control energy balance.